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‘The only good TB bacillus is a dead one’ – UCT’s Prof Valerie Mizrahi reflects on a world-leading career

‘The only good TB bacillus is a dead one’ – UCT’s Prof Valerie Mizrahi reflects on a world-leading career
Professor Valerie Mizrahi, a world-leading tuberculosis researcher and director of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, is retiring at the end of the year. (Photo: Nasief Manie / Spotlight)

Professor Valerie Mizrahi, a world-leading tuberculosis researcher and director of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, is retiring at the end of the year. Biénne Huisman sat down with Mizrahi to talk about her journey in TB research, passing the baton to a new generation of researchers, and how she helped build a research ecosystem that brings together specialists across the basic, clinical and public health sciences.

World-leading tuberculosis researcher Professor Valerie Mizrahi was 35 when her mother Etty started losing weight and coughing furiously. After healthcare professionals in Johannesburg failed to accurately diagnose her, it was a doctor in Plettenberg Bay who told Etty: “The good news is you don’t have lung cancer, the bad news is that you have tuberculosis (TB).”

At the time, Mizrahi’s two infant daughters – aged one and three years – had been spending much time with their granny, so Mizrahi found herself crushing TB prevention tablets into their porridge with honey.

Etty was treated at the then Rietfontein Hospital, the precursor to the Sizwe Tropical Diseases Hospital in Johannesburg. “My mom got very ill,” recalls Mizrahi. “She almost died of TB. And then 10 years later, she had to have a lobe from one of her lungs removed because she was one of those unfortunate people who got post-TB fibrosis.”

This was the early 1990s. Mizrahi was then with the South African Institute for Medical Research (SAIMR) linked to the University of the Witwatersrand, where she established the Molecular Biology Unit. She had identified TB as a lurking problem in South Africa, particularly in mines and in hospitals, calling it “a worthy foe ripe with opportunity for scientific investigation” – a problem she felt not enough people were talking about. It had been a pivotal moment when TB entered her own home, one that she says galvanised her thinking.

“It was a dramatic eye-opener for me as a basic scientist,” she says. “It was traumatic because of the time it happened in my career. Our family suddenly being thrust into the world of TB control. We had all these questions, like we didn’t know where my mum got it, was her TB drug-susceptible, and why it would take so long to find this out. I got to see first-hand how difficult it was to get answers.”

Prof Valerie Mizrahi

In the early 1990s Professor Valerie Mizrahi established the Molecular Biology Unit at the South African Institute for Medical Research linked to the University of the Witwatersrand. (Photo: Nasief Manie / Spotlight)

Born in 1958 to Etty and Morris in Harare, Zimbabwe, Mizrahi studied at the University of Cape Town (UCT), forging an unusual career path, veering from mathematics and chemistry to biochemistry, genetics and microbiology. In a male-dominated field, she became one of the first in South Africa to interrogate TB at a basic science level – that is, research aimed at advancing our understanding of the basic science of how TB bacteria survive, replicate and resist attempts to kill it.

Kill it ‘stone-cold dead’

Discussing TB, Mizrahi’s passion is effervescent, her every second sentence punctuated with “okay”. These underscore her statements – subtle pauses allowing for her preceding words to sink in.

A particular interest for Mizrahi is developing antibiotics “that can kill this bacterium stone-cold dead”.

“To me, the only good TB bacillus is a dead one,” she says. “But there’s a reason why TB has persisted for so long. The bacillus is pretty hard to kill. It’s built like Fort Knox. So it’s a monumental challenge. We don’t know where all the bacteria are residing. We know that TB in an infected lung is sitting in really difficult places, hard places for drugs to get to. This notion of going after the bacillus with drugs and just slamming it is a tough problem. Not insurmountable, but there’s a lot of research that needs to be done.”

TB can be cured, but treatment typically takes at least six months and involves taking at least four different antibiotics, with side-effects ranging from minor to serious. In addition to research on new antibiotics, there are also several experimental TB vaccines currently in late-phase studies. The only TB vaccine we have was developed more than a century ago and only has some moderate efficacy in kids.

The IDM

Since 2011 Mizrahi has served as director of the Institute of Infectious Disease and Molecular Medicine (IDM), UCT’s largest cross-faculty research unit with more than 800 affiliated staff and grants running into hundreds of millions of rands.

Mizrahi’s glass-encased office looks directly onto Table Mountain and Hospital Bend – where, at the time of our interview, N2 traffic out of Cape Town is already at a standstill. Behind her desk, Mizrahi quips: “Yes, this is the most beautiful office at UCT, everyone agrees.” Below, students are milling about on the health sciences campus.

If you are the kind of researcher who revels in asking questions and finding people who can answer them, then this is the place for you.

In 2022, in its Best Global Universities 2022-2023 survey, online portal US News ranked UCT as the 24th-best university in the world for studying infectious diseases. Mizrahi is ambivalent about the IDM taking credit for this accolade. She notes that this success is founded on problems of a “confounding and overwhelming” scope, with many diseases being proxies for poverty and inequality in South Africa.

The IDM’s focus includes TB, HIV/Aids, Covid-19, other infectious diseases like sexually transmitted infections, and noncommunicable diseases such as preventable cancers, cardiovascular, and psychiatric disorders.

Prof Valerie Mizrahi

The IDM that Mizrahi heads focuses on tuberculosis, HIV/Aids, Covid-19, other infectious diseases like sexually transmitted infections, and noncommunicable diseases such as preventable cancers, cardiovascular, and psychiatric disorders. (Photo: Nasief Manie / Spotlight)

Reflecting on the IDM, she says they have accrued a “research ecosystem – a concentration of expertise, something resembling critical mass” – bringing together specialists across the basic, clinical and public health sciences, in one place.

“We’ve got Groote Schuur Hospital across the road,” she says. “We have geneticists and biochemists, virologists and immunologists. There’s a clinician across the corridor from me, bioinformaticians, and microscopists downstairs. If you are the kind of researcher who revels in asking questions and finding people who can answer them, then this is the place for you.”

Multidisciplinary research is what excites her now. “HIV and TB have been so dominant in the narrative of this country. But now when you look at the figures and the data, we are dealing with a huge burden of noncommunicable disease on top of infectious diseases,” she says. “The key question moving forward is how not to think in silos.”

Polymaths and dilettantes

This, she says, takes humility.

“To do this, one has to be very humble. You need to know what you don’t know. People who work really well in interdisciplinary spaces are those who understand the limits of their own specialist knowledge, and the need to listen to where another person is coming from.”

She distinguishes between polymaths and dilettantes. “You have to be careful not to be a dilettante, who knows a little about a lot. Research can be very superficial in that way. So I have my antenna out all the time to distinguish between polymaths, who really are people who know a lot about a lot, and dilettantes, who know a little about a lot. And well, in this institute we have a lot of polymaths, brilliant researchers who move across disciplines, very interesting people to work with.”

Now it’s about opening up opportunities for others, writing a few papers, and contributing to the TB drug discovery space.

With a string of awards and an A1-rating from South Africa’s National Research Foundation, earlier this year, Mizrahi was elected a fellow of the Royal Society, the UK’s national academy of sciences. However, she recalls humbling moments along the way – like the time she flew to London seven months’ pregnant with her second child, for her first interview with the Wellcome Trust committee to secure funding. “I was so confident, but I was ill-prepared,” she says. “They savaged me! I tried to frame it not as a failure but as a learning experience.”

Passing the baton

At the end of this year Mizrahi will pass on the baton when she retires. Of her achievements, she is proudest of young scholars she has helped to shape. “Their legacies will last much longer than a few more citations of a publication,” she says.

Mizrahi notes more and more women leaders in her field. For example, recently, while delivering a talk at the Weizmann Institute in Israel, she noticed chemist and Nobel laureate Ada Yonath in the room. “Talk about a role model; I was almost in tears.”

Studying at UCT, Mizrahi’s own mentors had mostly been men – something she didn’t even notice, she says, as male professors treated her no differently. What did cut her was racial segregation at the time, prompting a political awakening and stints leaving South Africa to work in the US. First as a postdoctoral fellow at Pennsylvania State University and then at drug company SmithKline & French in Philadelphia.

Read more in Daily Maverick: The good doctor – Mark Blaylock on finding meaning back at Manguzi Hospital

Her own background makes her sensitive to marginalised groups, she says. Her grandparents were Sephardi Jews who fled Rhodes Island, today part of Greece, 10 years before World War 2, to find refuge in Zimbabwe.

Having just read former UCT vice-chancellor Max Price’s book Statues and Storms: Leading a University Through Change, she says: “It took me back to some very difficult times. It’s harrowing and brave and made me realise that even though I was here in the midst of it [#feesmustfall and #rhodesmustfall protests], a senior person of the university, how little I really knew of what was going on. It really is a lesson in crisis leadership.”

Earlier this year, Mizrahi was elected a fellow of the Royal Society, the UK’s national academy of sciences. (Photo: Nasief Manie / Spotlight)

Mizrahi lives in Sea Point with her one daughter. Her other daughter is based in Vancouver. Here, she likes to park her car at the end of the week, walking around, “either listening to a New York Times podcast or a beautiful piece of music and that’s when I think”.

She describes herself as an introvert who needs personal time to stay sane. She is deeply thoughtful about her roots, wondering about a sense of belonging. “As white people in Africa, I think this is part of the reckoning we go through. I truly identify as being African. Arriving at Johannesburg, just breathing in the air, it feels like home.”

Read more in Daily Maverick: Dr Lebogang Phahladira’s journey from studying by candlelight to winning a major schizophrenia research award

Looking back, Mizrahi notes her mother as a major influence in her life. “Not a highly educated woman. But the wisest, smartest person I know.” Etty still lives in Johannesburg while Morris has passed away. To this day, Etty thinks of herself as a proud TB survivor, says Mizrahi.

On her retirement, the scholar says: “Now it’s about opening up opportunities for others, writing a few papers, and contributing to the TB drug discovery space.”

“I’ve done the best I can,” she says, “I don’t believe in having regrets… There’s no control experiment to life, you can’t go back and redo it. But I don’t know that I could have done it any differently.” DM

This article was published by Spotlight – health journalism in the public interest.

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